CRAVING AND SENSITIZATION MODELS IN INBRED MICE STRAINS

产品说明：（改编自申请人的摘要）：所提出的研究旨在开发小鼠中药物渴望的行为实验室模型，并鉴定由遗传禀赋差异产生的渴望行为的个体差异。第一个具体目标是用两种近交系（Balb/c和C57 B1/6）和一种远交系（CD-1）小鼠来检查奖励寻求/自我施用范例。这些初步的研究将确定最佳参数测量渴望相关的行为在解决第二和第四个目标。我们的第二个目标是使用乙醇奖励、消耗乙醇的C57 Bl/6小鼠和抗渴望药物纳洛酮来测试药物寻求/口服自我给药程序。第三个目标是在一种新型的力板运动分析仪中完成，是表征可卡因和安非他明在相同的三种小鼠品系中的致敏和条件药物效应。根据当代药物滥用理论，致敏和条件性药物效应是渴望和复发的关键因素，我们使用力板传感器的初步数据表明，条件性药物效应和致敏在行为的空间和时间模式方面都是可测量的。第四个主要目标是开发一种混合装置，它结合了操作方法和测力板传感器，从而可以同时用两种方法研究寻求奖励的行为。在实现第四个目标时，将使用所有三种小鼠品系。在这些研究中，我们将应用最先进的计算机记录技术来测量涉及奖赏寻求和自我给药的工具性反应的物理特征，并量化品系特异性致敏和条件性药物反应。开发这样的动物模型将提供一些基本信息，以了解环境背景、遗传禀赋的个体差异和药理学变量如何影响药物渴望、药物寻求和最终药物服用。此外，未来的工作与这些方法应导致更有效的临床前评估的潜在有效的治疗和预防药物渴望的各种滥用药物的策略。

DESCRIPTION: (Adapted From The Applicant's Abstract): The proposed research aims to develop a behavioral laboratory model of drug craving in the mouse and to identify individual differences in craving behavior produced by differences in genetic endowment. The first specific goal is to examine a reward-seeking/self- administration paradigm with two inbred strains (Balb/c and C57Bl/6) and one outbred (CD-1) strain of mice. These initial studies will identify optimal parameters for measuring craving- related behaviors in addressing the second and fourth goals. Our second goal is to test the drug-seeking/ oral self-administration procedure using ethanol reward, the ethanol-consuming C57Bl/6 mice, and the anti-craving medication naltrexone. The third goal, to be accomplished in a new type of force plate movement analyzer, is to characterize sensitization and conditioned drugs effects of cocaine and amphetamine in the same three strains of mice. According to contemporary theories of drug abuse, sensitization and conditioned drug effects are key factors in craving and relapse, and our preliminary data with the force plate sensor suggest that conditioned drug effects and sensitization are measurable in terms of both spatial and temporal patterns of behavior. A fourth major goal is to develop a hybrid apparatus that incorporates both the operant methods and the force plate sensor so that reward-seeking behavior can be studied with both methods concurrently. In accomplishing the fourth goal all three strains of mice will be used. Throughout these studies, we will apply state-of-the-art computer recording techniques to the measurement of the physical characteristics of the instrumental response involved in reward- seeking and self-administration and quantify strain-specific sensitization and conditioned drug responses. Developing an animal model, such as this, will provide some of the basic information needed to understand how environmental context, individual differences in genetic endowment, and pharmacological variables influence drug craving, drug seeking and ultimately drug taking. In addition, future work with these methods should result in more effective pre-clinical evaluation of potentially effective treatment and prevention strategies of drug craving for a variety of abused drugs.